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Successful Orthotopic Heart Transplant in an Infant With an Inflammatory Myofibroblastic Tumor of the Left Ventricle
Successful Orthotopic Heart Transplant in an Infant With an Inflammatory Myofibroblastic Tumor of the Left Ventricle Michael V. Di Maria, MD,a David N. Campbell, MD,b Maxwell B. Mitchell, MD,b Mark A. Lovell, MD,c Biagio A. Pietra, MD,d and Shelley D. Miyamoto, MDd A female infant was diagnosed with an inflammatory myofibroblastic tumor involving the left ventricle, which compromised cardiac function. The tumor was endocardial in location and resection was not possible. In this study we report the first successful cardiac transplant and long-term follow-up for this indication. J Heart Lung Transplant 2008;27:792– 6. Copyright © 2008 by the International Society for Heart and Lung Transplantation.
Primary cardiac tumors are extremely rare in infants and children, with a prevalence of ⬍0.1%.1 The majority of cardiac tumors in children are benign, present in infancy, and consist of rhabdomyomas, followed by fibromas.2 Inflammatory myofibroblastic tumors (IMTs) of the heart are extremely uncommon, occurring primarily in children and young adults. Reports of cardiac IMTs consist of case reports and small series.3–10 The exact IMT incidence has not been well described due to the lesion’s rarity and a still-evolving understanding of its histologic properties. The tumor occurs more frequently in the organs and soft tissues of the thorax and abdomen than in the heart.11 This report describes the first successful cardiac transplantation of an infant with intracardiac IMT. CASE REPORT A 3-month-old infant girl presented to a local hospital emergency room with a low-grade fever and cough. In retrospect, the parents noted that tachypnea and increased effort of breathing had been intermittently present since birth. The infant was born at full term after an uncomplicated pregnancy and delivery. She had been feeding less vigorously and was being monitored for failure to thrive but was on no medications. Family history was remarkable for the mother and maternal grandmother having uterine fibroids and a maternal uncle with a pituitary tumor.
From the Departments of aPediatrics, bCardiovascular Surgery, cPathology and dCardiology, University of Colorado at Denver and Health Sciences Center, The Children’s Hospital, Aurora, Colorado. Submitted December 17, 2007; revised March 6, 2008; accepted March 12, 2008. Reprint requests: Shelley Miyamoto, MD, Department of Pediatrics, University of Colorado at Denver and Health Sciences Center, The Children’s Hospital, 13123 East 16th Avenue, B100, Aurora, CO 80045. Telephone: 720-777-5682. Fax: 720-777-7290. E-mail: miyamoto. [email protected] Copyright © 2008 by the International Society for Heart and Lung Transplantation. 1053-2498/08/$–see front matter. doi:10.1016/ j.healun.2008.03.005
792
Chest X-ray revealed an enlarged cardiothymic silhouette (Figure 1A). A transthoracic echocardiogram demonstrated a large mass on the left ventricular free wall, extending into the pericardial space (Figure 2A, B). Ventricular function was normal but a large pericardial effusion was present. Chest and abdominal computed tomography (CT) scans confirmed that the mass was adherent to the left ventricle; no other masses were identified (Figure 1B). She was taken to the operating room for pericardial drainage and biopsy of the tumor through a median sternotomy. On direct visualization, the coronary arteries were noted to course over the surface of the tumor making safe resection impossible. After pericardial drainage and low-dose inotropic support the patient had a marked improvement in clinical symptoms. Biopsy results were diagnostic for IMT and she was referred to our institution for transplant consideration. At the time of transfer, she was 4 months old and was on milrinone at 0.5 g/kg/min, digoxin and lasix. After extensive evaluation revealed no evidence of systemic involvement or end-organ dysfunction she was deemed to be an acceptable candidate and was listed for transplant. Serial echocardiograms demonstrated that the mass was increasing in size with distortion of the mitral annulus, resulting in moderate mitral regurgitation and mild mitral stenosis (5 mm Hg mean gradient) (Figure 2C, D). Although there was some flow acceleration noted in the left ventricular outflow tract, there was no obstruction. One week after being listed she was noted to have premature atrial contractions (PACs), unifocal premature ventricular contractions (PVCs) and several runs of non-sustained ventricular tachycardia. No electrolyte abnormalities were identified and she was clinically stable during these episodes. Amiodarone therapy was initiated and digoxin discontinued with a marked improvement in the frequency of PACs and PVCs and complete resolution of the ventricular tachycardia. She continued to feed ad libitum by mouth and gained approximately 20 g/day. She did
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Figure 1. A. Chest radiograph demonstrating enlarged cardiac silhouette. B. CT scan of the chest with contrast: Contiguous axial CT images at 3 mm increments were reconstructed through the chest. There is a large soft tissue density filling defect adjacent to the left ventricle which measured approximately 4.8 ⫻ 3.4 ⫻ 5.4 cm. * Represents tumor location.
not have any serious infections or complications while awaiting transplantation. At 103 days after being listed, a suitable donor organ became available. During the transplant, the recipient’s native heart fibrillated easily and she required several rounds of cardioversion during the dissection portion of the transplant operation. The size of the mass made it difficult to extract through the sternotomy incision. The surgeon described the tumor as fleshy and firm. The donor heart was sewn into position in standard fashion with atrial anastomosis; she was weaned from cardiopulmonary bypass and returned to the cardiac intensive care unit without complication. The tumor had clean margins and, although the left ventricular cavity was partially occupied by the tumor, it did not obstruct the left ventricular outflow tract (Figure 3A). Interestingly, the tumor did not extend through the endocardium. Histology confirmed the diagnosis of IMT (Figure 3B).3,5,12 Tumor cells were spindled with elongated nuclei. Areas of focal collections of chronic inflammatory cells (lymphocytes and plasma cells) and small calcifications were seen. No mitotic activity was recognized and the tumor was strongly immunopositive for smooth muscle actin and vimentin, but negative for anaplastic lymphoma kinase (ALK). The patient was extubated 24 hours after transplant and was off inotropes by Day 4 post-transplant. Induction consisted of high-dose steroids and polyclonal T-cell antibody (anti-thymocyte globulin). She was discharged from the hospital on Day 8 post-transplant with
maintenance immunosuppression of cyclosporine and mycophenolate mofetil. The patient is currently 3 years old and is developing normally with single-drug immunosuppression (cyclosporine). She has never received maintenance steroids as part of her immunosuppressive regimen, has had no episodes of rejection, and has not had a recurrence of the tumor. DISCUSSION We have described an infant who presented with signs and symptoms of heart failure secondary to a large cardiac tumor. Based on serial echocardiograms, the tumor was noted to increase in size over a period of weeks, causing increased mitral valve dysfunction (stenosis and regurgitation) and cardiac arrhythmias requiring medical management. The tumor was considered unresectable and diagnosed by biopsy as an inflammatory myofibroblastic tumor. IMFT in the heart is a rare, “benign” lesion, the treatment of which has traditionally involved resection of the mass. The benign nature of this tumor is belied by its propensity for occupying the cardiac lumen and its potential for embolization.10 In most descriptions of intracardiac IMT location, including the Burke series, which is the largest series to date of cardiac IMTs, tumors have been described as endocardial-based.3,10 The tumor in the case presented herein is quite unique in that the mass was not intraluminal but intramural and was associated with arrhythmias and distortion of the mitral valve, but did not result in embolic symptoms, like those seen in the more
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The Journal of Heart and Lung Transplantation July 2008
Figure 2. A. Echocardiographic apical 4 chamber view of the heart demonstrating the large cardiac mass (*) involving the lateral free wall of the left ventricle. LA, left artium; LV, left ventricle. B. Parasternal short axis view again demonstrating a large mass extending posterior to the left ventricle (measuring 54 ⫻ 46 ⫻ 36 mm). Note the mixed echogenicity of the mass throughout. C. Apical 4 chamber view demonstrating moderate regurgitation of the mitral valve. D. Apical 4 chamber view demonstrating mild stenosis of the mitral valve as evidenced by color aliasing of the mitral inflow.
typical filiform or peduncular morphology, which have been reported most frequently.10 Historically, IMTs have been postulated to arise secondary to immune or inflammatory dysregulation or an exaggerated response to tissue injury and have also been referred to as “inflammatory pseudotumor” or “plasma cell granuloma.”5,11,13 Post-viral cell-cycle disruption has been postulated as an alternative etiology. However, extracardiac IMT assays for evidence of human herpesvirus-8 (HHV-8) and Epstein–Barr virus (EBV) infection via polymerase chain reaction have not demonstrated a clear association.14 There is some preliminary evidence that the extracardiac tumor cells are clonal and therefore represent a true neoplasm. Fluorescent in situ hybridization of a series of IMTs revealed a common chromosomal abnormality on 2p23, involving the ALK gene.15
The presentation of the tumor seems to be related to tumor size and location, rather than malignant potential. Several investigators have reported constitutional symptoms, including fever, anemia, vasculitis and arthritis, occurring in the context of the tumor, which resolve after tumor resection.5,10 Although the tumor is biologically benign and rarely if ever metastatic, its intracardiac location can result in syncope, myocardial infarction or even sudden death.10 The diagnosis can be challenging and is based on the pathology of the tumor. Histologic characterization of IMT includes myofibroblastic spindle cells, a myxoid background, sparse mitotic activity with limited aneuploidy among the myofibroblasts, chronic inflammatory cell infiltrate (normally plasma cells or lymphocytes), positive smooth muscle actin staining, positive vimentin staining and variable positivity (⬃18% to 30%) for
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Figure 3. A. Gross photo of the explanted heart. Again, the tumor is denoted (*). Location with respect to the left ventricle (LV) and mitral valve (MV) annulus are well demonstrated. B. Hematoxylin and eosin staining of the tumor. Myofibroblastic spindle cells accompanied by lymphocytes and plasma cells infiltrate the cardiac muscle (original magnification 400X).
anaplastic lymphoma kinase (ALK).14,16 –18 ALK expression may confer a better prognosis, similarly to the neoplasm in which the protein was first identified, anaplastic large-cell lymphoma.16 Treatment options vary depending on location and associated symptoms. In contrast to the more common rhabdomyomas, which spontaneously regress, complete surgical resection of cardiac IMTs is the treatment of choice and can be curative.11 Steroids, chemotherapy and radiation have all been utilized, primarily as adjunctive therapy in those patients with unresectable or incompletely resected tumors.11,13 Tumor recurrence is rare (8% overall), but may be more likely if tumor resection is incomplete and adjuvant therapy is
not administered.11 The only reported recurrence in cardiac IMT occurred in an infant following surgical resection.19 It is unclear from that report whether positive surgical margins were achieved. In another case, multiple IMTs were discovered in the right ventricle of a 2-month-old boy treated with sub-total resection secondary to tumor location, with no adjunctive therapy given.9 The investigators indicated no recurrence of the tumor, but follow-up was short. In another report, a spontaneous 40% reduction in size was noted to occur over an 11-month period in a child with an inoperable cardiac IMT, suggesting conservative observation alone may be an option in some patients.7 The inability to predict which IMTs are likely to
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spontaneously resolve increases the risk of this approach.5,10,17 When resection of cardiac IMT is not possible secondary to association of the tumor to vital structures, the only viable option may be cardiac transplantation. In light of the improving outcome of infant and child heart transplantation, the transplant option should be considered for this rare problem.20 The case presented herein provides the first description of a successful heart transplant in an infant with an unresectable cardiac IMT. The patient currently has normal graft function and is without evidence of tumor recurrence 3 years post-transplant. REFERENCES 1. Nadas AS, Ellison RC. Cardiac tumors in infancy. Am J Cardiol 1968;21:363– 6. 2. Freedom RM, Lee KJ, MacDonald C, Taylor G. Selected aspects of cardiac tumors in infancy and childhood. Pediatr Cardiol 2000; 21:299 –316. 3. de Montpreville VT, Serraf A, Aznag H, et al. Fibroma and inflammatory myofibroblastic tumor of the heart. Ann Diagn Pathol 2001;5:335– 42. 4. Gandy KL, Burtelow MA, Reddy VM, Silverman NH. Myofibroblastic tumor of the heart: a rare intracardiac tumor. J Thorac Cardiovasc Surg 2005;130:888 –9. 5. Li L, Cerilli LA, Wick MR. Inflammatory pseudotumor (myofibroblastic tumor) of the heart. Ann Diagn Pathol 2002;6:116 –21. 6. Murdison KA, Septimus S, Garola RE, Pizarro C. Intracardiac inflammatory myofibroblastic tumor: a unique presentation. Eur J Cardiothorac Surg 2007;31:750 –2. 7. Pearson PJ, Smithson WA, Driscoll DJ, Banks PM, Ehman RL. Inoperable plasma cell granuloma of the heart: spontaneous decrease in size during an 11-month period. Mayo Clin Proc 1988;63:1022–5. 8. Su JW, Caleb MG, Tan RS, Low AF, Lim CH. Cardiac inflammatory myofibroblastic tumor as a rare cause of aortic regurgitation: a case report. J Thorac Cardiovasc Surg 2006;132:150 –1.
The Journal of Heart and Lung Transplantation July 2008
9. Tian JT, Cheng LC, Yung TC. Multiple cardiac inflammatory myofibroblastic tumors in the right ventricle in an infant. Ann Thorac Surg 2006;82:1531–5. 10. Burke A, Li L, Kling E, et al. Cardiac Inflammatory myofibroblastic tumor: a “benign” neoplasm that may result in syncope, myocardial infarction, and sudden death. Am J Surg Pathol 2007;31: 1115–22. 11. Kovach SJ, Fischer AC, Katzman PJ, et al. Inflammatory myofibroblastic tumors. J Surg Oncol 2006;94:385–91. 12. Hill KA, Gonzalez-Crussi F, Chou PM. Calcifying fibrous pseudotumor versus inflammatory myofibroblastic tumor: a histological and immunohistochemical comparison. Mod Pathol 2001;14: 784 –90. 13. Ferbend P, Abramson LP, Backer CL, et al. Cardiac plasma cell granulomas: response to oral steroid treatment. Pediatr Cardiol 2004;25:406 –10. 14. Mergan F, Jaubert F, Sauvat F, et al. Inflammatory myofibroblastic tumor in children: clinical review with anaplastic lymphoma kinase, Epstein–Barr virus, and human herpesvirus 8 detection analysis. J Pediatr Surg 2005;40:1581– 6. 15. Griffin CA, Hawkins AL, Dvorak C, et al. Recurrent involvement of 2p23 in inflammatory myofibroblastic tumors. Cancer Res 1999;59:2776 – 80. 16. Chun YS, Wang L, Nascimento AG, Moir CR, Rodeberg DA. Pediatric inflammatory myofibroblastic tumor: anaplastic lymphoma kinase (ALK) expression and prognosis. Pediatr Blood Cancer 2005;45:796 – 801. 17. Sebire NJ, Ramsay A, Sheppard M, et al. Intravascular inflammatory myofibroblastic tumors in infancy. Pediatr Dev Pathol 2002; 5:400 – 4. 18. Tavora F, Shilo K, Ozbudak IH, et al. Absence of human herpesvirus-8 in pulmonary inflammatory myofibroblastic tumor: immunohistochemical and molecular analysis of 20 cases. Mod Pathol 2007;20:955–9. 19. Hartyanszky IL, Kadar K, Hubay M. Rapid recurrence of an inflammatory myofibroblastic tumor in the right ventricular outflow tract. Cardiol Young 2000;10:271– 4. 20. Ross M, Kouretas P, Gamberg P, et al. Ten- and 20-year survivors of pediatric orthotopic heart transplantation. J Heart Lung Transplant 2006;25:261–70.
Primary cardiac tumors are extremely rare in infants and children, with a prevalence of ⬍0.1%.1 The majority of cardiac tumors in children are benign, present in infancy, and consist of rhabdomyomas, followed by fibromas.2 Inflammatory myofibroblastic tumors (IMTs) of the heart are extremely uncommon, occurring primarily in children and young adults. Reports of cardiac IMTs consist of case reports and small series.3–10 The exact IMT incidence has not been well described due to the lesion’s rarity and a still-evolving understanding of its histologic properties. The tumor occurs more frequently in the organs and soft tissues of the thorax and abdomen than in the heart.11 This report describes the first successful cardiac transplantation of an infant with intracardiac IMT. CASE REPORT A 3-month-old infant girl presented to a local hospital emergency room with a low-grade fever and cough. In retrospect, the parents noted that tachypnea and increased effort of breathing had been intermittently present since birth. The infant was born at full term after an uncomplicated pregnancy and delivery. She had been feeding less vigorously and was being monitored for failure to thrive but was on no medications. Family history was remarkable for the mother and maternal grandmother having uterine fibroids and a maternal uncle with a pituitary tumor.
From the Departments of aPediatrics, bCardiovascular Surgery, cPathology and dCardiology, University of Colorado at Denver and Health Sciences Center, The Children’s Hospital, Aurora, Colorado. Submitted December 17, 2007; revised March 6, 2008; accepted March 12, 2008. Reprint requests: Shelley Miyamoto, MD, Department of Pediatrics, University of Colorado at Denver and Health Sciences Center, The Children’s Hospital, 13123 East 16th Avenue, B100, Aurora, CO 80045. Telephone: 720-777-5682. Fax: 720-777-7290. E-mail: miyamoto. [email protected] Copyright © 2008 by the International Society for Heart and Lung Transplantation. 1053-2498/08/$–see front matter. doi:10.1016/ j.healun.2008.03.005
792
Chest X-ray revealed an enlarged cardiothymic silhouette (Figure 1A). A transthoracic echocardiogram demonstrated a large mass on the left ventricular free wall, extending into the pericardial space (Figure 2A, B). Ventricular function was normal but a large pericardial effusion was present. Chest and abdominal computed tomography (CT) scans confirmed that the mass was adherent to the left ventricle; no other masses were identified (Figure 1B). She was taken to the operating room for pericardial drainage and biopsy of the tumor through a median sternotomy. On direct visualization, the coronary arteries were noted to course over the surface of the tumor making safe resection impossible. After pericardial drainage and low-dose inotropic support the patient had a marked improvement in clinical symptoms. Biopsy results were diagnostic for IMT and she was referred to our institution for transplant consideration. At the time of transfer, she was 4 months old and was on milrinone at 0.5 g/kg/min, digoxin and lasix. After extensive evaluation revealed no evidence of systemic involvement or end-organ dysfunction she was deemed to be an acceptable candidate and was listed for transplant. Serial echocardiograms demonstrated that the mass was increasing in size with distortion of the mitral annulus, resulting in moderate mitral regurgitation and mild mitral stenosis (5 mm Hg mean gradient) (Figure 2C, D). Although there was some flow acceleration noted in the left ventricular outflow tract, there was no obstruction. One week after being listed she was noted to have premature atrial contractions (PACs), unifocal premature ventricular contractions (PVCs) and several runs of non-sustained ventricular tachycardia. No electrolyte abnormalities were identified and she was clinically stable during these episodes. Amiodarone therapy was initiated and digoxin discontinued with a marked improvement in the frequency of PACs and PVCs and complete resolution of the ventricular tachycardia. She continued to feed ad libitum by mouth and gained approximately 20 g/day. She did
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Figure 1. A. Chest radiograph demonstrating enlarged cardiac silhouette. B. CT scan of the chest with contrast: Contiguous axial CT images at 3 mm increments were reconstructed through the chest. There is a large soft tissue density filling defect adjacent to the left ventricle which measured approximately 4.8 ⫻ 3.4 ⫻ 5.4 cm. * Represents tumor location.
not have any serious infections or complications while awaiting transplantation. At 103 days after being listed, a suitable donor organ became available. During the transplant, the recipient’s native heart fibrillated easily and she required several rounds of cardioversion during the dissection portion of the transplant operation. The size of the mass made it difficult to extract through the sternotomy incision. The surgeon described the tumor as fleshy and firm. The donor heart was sewn into position in standard fashion with atrial anastomosis; she was weaned from cardiopulmonary bypass and returned to the cardiac intensive care unit without complication. The tumor had clean margins and, although the left ventricular cavity was partially occupied by the tumor, it did not obstruct the left ventricular outflow tract (Figure 3A). Interestingly, the tumor did not extend through the endocardium. Histology confirmed the diagnosis of IMT (Figure 3B).3,5,12 Tumor cells were spindled with elongated nuclei. Areas of focal collections of chronic inflammatory cells (lymphocytes and plasma cells) and small calcifications were seen. No mitotic activity was recognized and the tumor was strongly immunopositive for smooth muscle actin and vimentin, but negative for anaplastic lymphoma kinase (ALK). The patient was extubated 24 hours after transplant and was off inotropes by Day 4 post-transplant. Induction consisted of high-dose steroids and polyclonal T-cell antibody (anti-thymocyte globulin). She was discharged from the hospital on Day 8 post-transplant with
maintenance immunosuppression of cyclosporine and mycophenolate mofetil. The patient is currently 3 years old and is developing normally with single-drug immunosuppression (cyclosporine). She has never received maintenance steroids as part of her immunosuppressive regimen, has had no episodes of rejection, and has not had a recurrence of the tumor. DISCUSSION We have described an infant who presented with signs and symptoms of heart failure secondary to a large cardiac tumor. Based on serial echocardiograms, the tumor was noted to increase in size over a period of weeks, causing increased mitral valve dysfunction (stenosis and regurgitation) and cardiac arrhythmias requiring medical management. The tumor was considered unresectable and diagnosed by biopsy as an inflammatory myofibroblastic tumor. IMFT in the heart is a rare, “benign” lesion, the treatment of which has traditionally involved resection of the mass. The benign nature of this tumor is belied by its propensity for occupying the cardiac lumen and its potential for embolization.10 In most descriptions of intracardiac IMT location, including the Burke series, which is the largest series to date of cardiac IMTs, tumors have been described as endocardial-based.3,10 The tumor in the case presented herein is quite unique in that the mass was not intraluminal but intramural and was associated with arrhythmias and distortion of the mitral valve, but did not result in embolic symptoms, like those seen in the more
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Di Maria et al.
The Journal of Heart and Lung Transplantation July 2008
Figure 2. A. Echocardiographic apical 4 chamber view of the heart demonstrating the large cardiac mass (*) involving the lateral free wall of the left ventricle. LA, left artium; LV, left ventricle. B. Parasternal short axis view again demonstrating a large mass extending posterior to the left ventricle (measuring 54 ⫻ 46 ⫻ 36 mm). Note the mixed echogenicity of the mass throughout. C. Apical 4 chamber view demonstrating moderate regurgitation of the mitral valve. D. Apical 4 chamber view demonstrating mild stenosis of the mitral valve as evidenced by color aliasing of the mitral inflow.
typical filiform or peduncular morphology, which have been reported most frequently.10 Historically, IMTs have been postulated to arise secondary to immune or inflammatory dysregulation or an exaggerated response to tissue injury and have also been referred to as “inflammatory pseudotumor” or “plasma cell granuloma.”5,11,13 Post-viral cell-cycle disruption has been postulated as an alternative etiology. However, extracardiac IMT assays for evidence of human herpesvirus-8 (HHV-8) and Epstein–Barr virus (EBV) infection via polymerase chain reaction have not demonstrated a clear association.14 There is some preliminary evidence that the extracardiac tumor cells are clonal and therefore represent a true neoplasm. Fluorescent in situ hybridization of a series of IMTs revealed a common chromosomal abnormality on 2p23, involving the ALK gene.15
The presentation of the tumor seems to be related to tumor size and location, rather than malignant potential. Several investigators have reported constitutional symptoms, including fever, anemia, vasculitis and arthritis, occurring in the context of the tumor, which resolve after tumor resection.5,10 Although the tumor is biologically benign and rarely if ever metastatic, its intracardiac location can result in syncope, myocardial infarction or even sudden death.10 The diagnosis can be challenging and is based on the pathology of the tumor. Histologic characterization of IMT includes myofibroblastic spindle cells, a myxoid background, sparse mitotic activity with limited aneuploidy among the myofibroblasts, chronic inflammatory cell infiltrate (normally plasma cells or lymphocytes), positive smooth muscle actin staining, positive vimentin staining and variable positivity (⬃18% to 30%) for
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Figure 3. A. Gross photo of the explanted heart. Again, the tumor is denoted (*). Location with respect to the left ventricle (LV) and mitral valve (MV) annulus are well demonstrated. B. Hematoxylin and eosin staining of the tumor. Myofibroblastic spindle cells accompanied by lymphocytes and plasma cells infiltrate the cardiac muscle (original magnification 400X).
anaplastic lymphoma kinase (ALK).14,16 –18 ALK expression may confer a better prognosis, similarly to the neoplasm in which the protein was first identified, anaplastic large-cell lymphoma.16 Treatment options vary depending on location and associated symptoms. In contrast to the more common rhabdomyomas, which spontaneously regress, complete surgical resection of cardiac IMTs is the treatment of choice and can be curative.11 Steroids, chemotherapy and radiation have all been utilized, primarily as adjunctive therapy in those patients with unresectable or incompletely resected tumors.11,13 Tumor recurrence is rare (8% overall), but may be more likely if tumor resection is incomplete and adjuvant therapy is
not administered.11 The only reported recurrence in cardiac IMT occurred in an infant following surgical resection.19 It is unclear from that report whether positive surgical margins were achieved. In another case, multiple IMTs were discovered in the right ventricle of a 2-month-old boy treated with sub-total resection secondary to tumor location, with no adjunctive therapy given.9 The investigators indicated no recurrence of the tumor, but follow-up was short. In another report, a spontaneous 40% reduction in size was noted to occur over an 11-month period in a child with an inoperable cardiac IMT, suggesting conservative observation alone may be an option in some patients.7 The inability to predict which IMTs are likely to
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spontaneously resolve increases the risk of this approach.5,10,17 When resection of cardiac IMT is not possible secondary to association of the tumor to vital structures, the only viable option may be cardiac transplantation. In light of the improving outcome of infant and child heart transplantation, the transplant option should be considered for this rare problem.20 The case presented herein provides the first description of a successful heart transplant in an infant with an unresectable cardiac IMT. The patient currently has normal graft function and is without evidence of tumor recurrence 3 years post-transplant. REFERENCES 1. Nadas AS, Ellison RC. Cardiac tumors in infancy. Am J Cardiol 1968;21:363– 6. 2. Freedom RM, Lee KJ, MacDonald C, Taylor G. Selected aspects of cardiac tumors in infancy and childhood. Pediatr Cardiol 2000; 21:299 –316. 3. de Montpreville VT, Serraf A, Aznag H, et al. Fibroma and inflammatory myofibroblastic tumor of the heart. Ann Diagn Pathol 2001;5:335– 42. 4. Gandy KL, Burtelow MA, Reddy VM, Silverman NH. Myofibroblastic tumor of the heart: a rare intracardiac tumor. J Thorac Cardiovasc Surg 2005;130:888 –9. 5. Li L, Cerilli LA, Wick MR. Inflammatory pseudotumor (myofibroblastic tumor) of the heart. Ann Diagn Pathol 2002;6:116 –21. 6. Murdison KA, Septimus S, Garola RE, Pizarro C. Intracardiac inflammatory myofibroblastic tumor: a unique presentation. Eur J Cardiothorac Surg 2007;31:750 –2. 7. Pearson PJ, Smithson WA, Driscoll DJ, Banks PM, Ehman RL. Inoperable plasma cell granuloma of the heart: spontaneous decrease in size during an 11-month period. Mayo Clin Proc 1988;63:1022–5. 8. Su JW, Caleb MG, Tan RS, Low AF, Lim CH. Cardiac inflammatory myofibroblastic tumor as a rare cause of aortic regurgitation: a case report. J Thorac Cardiovasc Surg 2006;132:150 –1.
The Journal of Heart and Lung Transplantation July 2008
9. Tian JT, Cheng LC, Yung TC. Multiple cardiac inflammatory myofibroblastic tumors in the right ventricle in an infant. Ann Thorac Surg 2006;82:1531–5. 10. Burke A, Li L, Kling E, et al. Cardiac Inflammatory myofibroblastic tumor: a “benign” neoplasm that may result in syncope, myocardial infarction, and sudden death. Am J Surg Pathol 2007;31: 1115–22. 11. Kovach SJ, Fischer AC, Katzman PJ, et al. Inflammatory myofibroblastic tumors. J Surg Oncol 2006;94:385–91. 12. Hill KA, Gonzalez-Crussi F, Chou PM. Calcifying fibrous pseudotumor versus inflammatory myofibroblastic tumor: a histological and immunohistochemical comparison. Mod Pathol 2001;14: 784 –90. 13. Ferbend P, Abramson LP, Backer CL, et al. Cardiac plasma cell granulomas: response to oral steroid treatment. Pediatr Cardiol 2004;25:406 –10. 14. Mergan F, Jaubert F, Sauvat F, et al. Inflammatory myofibroblastic tumor in children: clinical review with anaplastic lymphoma kinase, Epstein–Barr virus, and human herpesvirus 8 detection analysis. J Pediatr Surg 2005;40:1581– 6. 15. Griffin CA, Hawkins AL, Dvorak C, et al. Recurrent involvement of 2p23 in inflammatory myofibroblastic tumors. Cancer Res 1999;59:2776 – 80. 16. Chun YS, Wang L, Nascimento AG, Moir CR, Rodeberg DA. Pediatric inflammatory myofibroblastic tumor: anaplastic lymphoma kinase (ALK) expression and prognosis. Pediatr Blood Cancer 2005;45:796 – 801. 17. Sebire NJ, Ramsay A, Sheppard M, et al. Intravascular inflammatory myofibroblastic tumors in infancy. Pediatr Dev Pathol 2002; 5:400 – 4. 18. Tavora F, Shilo K, Ozbudak IH, et al. Absence of human herpesvirus-8 in pulmonary inflammatory myofibroblastic tumor: immunohistochemical and molecular analysis of 20 cases. Mod Pathol 2007;20:955–9. 19. Hartyanszky IL, Kadar K, Hubay M. Rapid recurrence of an inflammatory myofibroblastic tumor in the right ventricular outflow tract. Cardiol Young 2000;10:271– 4. 20. Ross M, Kouretas P, Gamberg P, et al. Ten- and 20-year survivors of pediatric orthotopic heart transplantation. J Heart Lung Transplant 2006;25:261–70.